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Biomedical subjects

D Paul

Publications and source records attributed to D Paul.

At least 181 records · Page 10Linked to original sources
PubMed1981

The neuromuscular and autonomic blocking effects of azasteroids containing choline or acetylcholine fragments.

Nine analogues of the azasteroid muscle relaxant chandonium have been tested for neuromuscular blocking activity, ganglion blocking activity, inhibitory effects on cardiac muscarinic receptors, and for effects on noradrenergic transmission. Experiments were performed in anaesthetized cats and in isolated preparations. The two bisquaternary compounds HS-626 and HS-627, choline and acetylcholine-like analogues of chandonium respectively, were approximately equipotent with chandonium as neuromuscular blocking agents in the cat, but HS-672 possessed slightly more vagal blocking action. No evidence was obtained for ganglion block. The monoquaternary analogues, HS-408 and HS-465 and two 4-aza-androstanes, (HS-522 and HS-523) were more than 100 times less active than the bisquaternary compounds as neuromuscular blocking agents, and produced vagal blockade and ganglion blockade at sub-neuromuscular blocking doses. pA2 determinations in the chick biventer cervicis muscle, the guinea-pig atria and guinea-pig ileum showed that the bisquaternary compounds chandonium, HS-626 and HS-627 were much more potent in blocking cardiac than intestinal muscarinic receptors and that HS-626 possessed the widest margin between concentrations blocking the nicotinic receptors at the neuromuscular junction and the cardiac muscarinic receptors. Evidence for the three bisquaternary compounds blocking neuronal noradrenaline reuptake was obtained only at very high concentrations. HS-626 possessed a slightly more desirable spectrum of activities than chandonium, but the degree of improvement over the parent compound is insufficient to merit extensive clinical testing.

Acetylcholine↗
PubMed1981

Sinus infection and adenotonsillitis in pediatric patients.

A number of children who suffer from tonsillitis and adenoids hypertrophy also have associated sinus infection. These patients, who are widely treated, have varied responses; hence a correlation has been sought between the two ailments. A study of 100 children between 1-12 years of age was undertaken to provide a correlation. Therapeutic response to the treatment of sinusitis, vis-a-vis adenotonsillitis, was noted. This work has been supplemented by experimental studies on dogs and conclusion has been drawn.

Adenoidectomy↗
PubMed1981

Preparation and specificities of antisera to the amino-terminal sequence of the carcinoembryonic antigen.

A tetracosapeptide (peptide-24) corresponding to the amino-terminal sequence of the carcinoembryonic antigen (CEA) was synthesized and characterized. Antisera were produced to the peptide-24, and a radioimmunoassay was developed utilizing peptide-24 with a tyrosine residue on the amino-terminal end (Tyr-peptide-24). Inhibitions of anti-peptide-24-125I-Tyr-peptide-24 complex formation were done with several preparations of CEA and the normal cross-reacting antigen. The extent of cross-reactivities was low, one CEA preparation requiring a 250-fold molar quantity greater than peptide-24 to obtain the same degree of inhibition. Attempts to degrade the CEAs and normal cross-reacting antigens in order to possibly expose the amino-terminal ends for reactivity with antibody did not result in any great increase in inhibitory capacity. It was concluded that either the conformations of the antigenic determinant(s) of the peptide-24 and of the amino-terminal end of CEA were sufficiently different to result in little cross-reacting antigen are blocked for reactivity with antibody by other portions of the molecule.

Amino Acid Sequence↗
PubMed1980

Stimulation of DNA synthesis any myo-inositol incorporation in mammalian cells.

Phosphatidylinositol (PI) synthesis and its role in controlling the cell cycle has been investigated using fibroblasts and liver cells in culture. PI synthesis as measured by incorporation of [3H]-myo-inositol into trichloroacetic acid precipitable material during 0--60 min after serum or growth factor stimulation of serum-starved cells is increased in primary fetal rat liver cells, rat embryo fibroblasts, and 3T3 mouse cells. In contrast, growth stimulation of 3T3 cells and hepatocytes rendered quiescent in G1 by amino acid starvation is not accompanied by increased incorporation of [3H[-myo-inositol into trichloroacetic acid precipitable material. This suggests that those cells might be arrested at a different point in G1 than cells arrested by serum depletion. Inhibition of PI synthesis by variation of-hexachlorocyclohexane (HCH), a steric analog of myo-inositol, during early times (e.g., 0--4 hr) after growth stimulation, reversibly blocks initiation of DNA synthesis in 3T3 cells. The results support the idea that increased PI synthesis in response to growth stimulation in the cell types studied here is a prerequisite for progression through G1 and subsequent entry into S phase.

Animals↗
PubMed1980

Human platelet basic protein associated with antiheparin and mitogenic activities: purification and partial characterization.

Platelet basic protein (PBP) (isoelectric point, 10.0-10.5; apparent Mr, 11,000-15,000) has been purified to homogeneity from material secreted by fresh human platelets after stimulation by thrombin. The purification, using preparative isoelectric focusing and chromatography on heparin-Sepharose, yielded two additional peptides with antiheparin activity that were immunologically identical with PBP: low-affinity platelet factor 4 and beta-thromboglubulin. The purity of the peptides was confirmed by immuoelectrophoresis and by NH2-terminal amino acid analysis. Dansyl chloride-treated PBP yielded a single dansylated amino acid residue (glycine). By using a specific radioimmunoassay it was shown that 10(9) human platelets contain 2-3 microgram of PBP which can be released in response to specific stimulation. PBP is associated with mitogenic activity as assayed in Swiss 3T3 mouse cells cultured in low-serum (0.4-1.5%) medium at levels of about 1 ng/ml and saturating at 10-40 ng/ml. The biological activity of different PBP preparations was variable, presumably due to inhibition by the varying amounts of ampholytes that interfered with the mitogenic activity of the peptide. Mitogenic activity was eluted from NaDodSO4/polyacrylamide gels and shown to comigrate with immunoreactive material and with conventional marker proteins of 14,000-17,000 daltons or with histones of 11,000-15,000 daltons. Evidence is presented that PBP is different from cationic platelet-derived growth factor which has an apparent Mr of 30,000.

Amino Acid Sequence↗
PubMed1980

Secreted platelet proteins with antiheparin and mitogenic activities in chronic renal failure.

The levels of secreted platelet antigen (LA-PF4/beta TG) were measured by radioimmunoassay in samples of PPP obtained from human blood collected on EDTA and inhibitors of platelet release reaction. These levels in plasma of 17 normal individuals, 18 nondialyzed patients with chronic renal failure, and nine patients on hemodialysis were 31.9 +/- 2.8 ng/ml, 135.1 +/- 21.4, and 291.8 +/- 26.3, respectively. No significant differences were observed in platelet counts and in the levels of this antigen in PRP of these three groups of individuals. The levels of PF4 in PPP of eight normal individuals and in plasma of seven patients with chronic renal failure were 7.41 +/- 0.67 and 7.53 +/- 1.11 ng/ml, respectively. During processing of blood samples in the absence of platelet release inhibitors, platelets of patients with chronic renal failure released less LA-PF4/beta TG antigen than did normal platelets. The mean levels of LA-PF4/beta TG antigen excreted in urine of six normal individuals and 10 patients with chronic renal failure were 57.75 and 1461.5 ng/100 mg of creatinine per day, respectively. After 3 hr hemodialysis, LA-PF4/beta TG antigen levels in PPP increased from 291.8 +/- 26.3 ng/ml to 505.3 +/- 87.3. By contrast, this antigen in three patients with successful kidney transplants rapidly returned to levels close to normal following graft function. Immunoreactive material from pooled urine of patients with chronic renal failure was isolated by isoelectric focusing. This material focused at pH 10.0 to 10.8 and induced DNA biosynthesis in 3(3 swiss cells, indicating its similarity to PBP. It is proposed that elevation of LA-PF4/beta TG antigen observed in plasma of patients with chronic renal failure resulted from the impaired handling of this protein by the kidney.

Adult↗
PubMed1979

Cell cycle control by Ca++-ions in mouse 3T3 cells and in transformed 3T3 cells.

Total cellular calcium levels do not change when 3T3-4a cells stop proliferating due to serum depletion, or when serum-arrested quiescent cells are incubated for up to 44 hours in calcium-deficient medium (approximately 10 micrometer Ca++). Upon stimulation with dialyzed serum cells enter S and progress through at least one cycle even at extremely low calcium levels in the culture medium (greater than or equal to 10 micrometer). Cells divide until a final cell density is attained which is proportional to the calcium concentration in the medium and cells reversibly arrest in G1. Cells which arrested in G1 in medium containing less than or equal to 26 micrometer Ca++ in the presence of excess serum can be stimulated to enter S in response to added calcium after a prereplicative phase of 14 to 16 hours. Serum does not affect 45Ca-uptake in these cells. Benzo[a]pyrene transformed 3T3 (BP3T3) cells have a 100--200 times lower Ca++-requirement than 3T3 cells but arrest in G1 at low Ca++ levels. In contrast, SV40-virus transformed 3T3 (SV3T3) cells that grow without restriction in monolayer cultures have even lower Ca++-requirements for growth than BP3T3 cells and have no Ca++-sensitive restriction point. Therefore, 3T3 and BP3T3 cells have retained the capacity to sense intracellular Ca++-pool sizes and to arrest in G1 at subthreshold cellular Ca++-levels.

Calcium↗